Anabolic-androgenic steroid hormones have recently been placed on the controlled substance list by the United States Food and Drug Administration primarily due to their abuse by male and female athletes. Reported deleterious effects on abusers include sterility, gynecomastia in males, acne, balding, psychological changes, and increased risks of heart disease and certain neoplasia. Considering the roles of the immune and neuroendocrine systems in many of these pathologies, it would be important to determine the effects of these derivatized androgens on those systems. At the high pharmacological doses at which the steroids are used, little is known in this respect. We have found, however, that the anabolic steroid nandrolone decanoate significantly affects the production of the hormone corticotropin from leukocytes. In addition, we have found that his same anabolic steroid enhances the production of the inflammatory cytokines interleukin-1 and tumor necrosis factor. Furthermore, interferon induction is altered in fibroblasts. Finally, when anabolic steroid-treated leukocytes are analyzed by computerized shape-factor analysis, a significant decrease in activation parameters is noted. The overall objective of this proposal, therefore, is to determine the effects of anabolic steroids on the immune and neuroendocrine systems and their interactions. Specifically, we propose to: 1) Determine the effects of anabolic steroids on the production of cytokines and hormones by human leukocytes in vitro; 2) Determine the effects of varying high pharmacological dosages of anabolic steroids on the production of cytokines and hormones by splenocytes harvested from short- and long-term treated mice; 3) Determine if anabolic steroids affect the immunological and antiviral effects of the adrenal androgen dehydroepiandrosterone (DHEA), which recently has been shown to have potent immunomodulatory, antiviral and anticancer effects; 4) Determine the effects of anabolic steroids on virulence, growth and metastasis of B-16 melanoma variants utilizing a mouse mode. These studies will provide information about the primary effects of high doses of anabolic steroids on the immune and neuroendocrine axis that could significantly influence the pathologies attributed to their abuse.